(2S,3R)-3-(((tert-butyldimethylsilyl)oxy)-4-(4-fluoro-N-methylphenylsulfonamido)-N-(2S)-1-((4-methoxybenzyl)oxy)propan-2-yl)-2-methylbutanamide | 1403480-06-7

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: (2S,3R)-3-(((tert-butyldimethylsilyl)oxy)-4-(4-fluoro-N-methylphenylsulfonamido)-N-(2S)-1-((4-methoxybenzyl)oxy)propan-2-yl)-2-methylbutanamide
• 英文别名: (2S,3R)-3-((tert-butyldimethylsilyl)oxy)-4-(4-fluoro-N-methylphenylsulfonamido)-N-((S)-1-((4-methoxybenzyl)oxy)propan-2-yl)-2-methylbutanamide；(2S,3R)-3-[tert-butyl(dimethyl)silyl]oxy-4-[(4-fluorophenyl)sulfonyl-methylamino]-N-[(2S)-1-[(4-methoxyphenyl)methoxy]propan-2-yl]-2-methylbutanamide
• CAS: 1403480-06-7
• 化学式: C₂₉H₄₅FN₂O₆SSi
• 分子量: 596.836
• InChiKey: IASNXRCXQRYYEM-BERHBOFZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.2
• 重原子数：
  40
• 可旋转键数：
  15
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.55
• 拓扑面积：
  103
• 氢给体数：
  1
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  (2S,3R)-3-(((tert-butyldimethylsilyl)oxy)-4-(4-fluoro-N-methylphenylsulfonamido)-N-(2S)-1-((4-methoxybenzyl)oxy)propan-2-yl)-2-methylbutanamide 在 dimethyl sulfide borane 、 四丁基氟化铵 、 sodium hydride 、 三乙胺 作用下， 以 四氢呋喃 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 55.25h， 生成 tert-butyl ((2R,3R)-3-(allyloxy)-4-(4-fluoro-N-methylphenylsulfonamido)-2-methylbutyl)((2S)-1-((4-methoxybenzyl)oxy)propan-2-yl)carbamate
  参考文献：
  名称：

  Diversity-Oriented Synthesis-Facilitated Medicinal Chemistry: Toward the Development of Novel Antimalarial Agents

  摘要：

  Here, we describe medicinal chemistry that was accelerated by a diversity-oriented synthesis (DOS) pathway, and in vivo studies of our previously reported macrocyclic antimalarial agent that derived from the synthetic pathway. Structure-activity relationships that focused on both appendage and skeletal features yielded a nanomolar inhibitor of P. falciparum asexual blood-stage growth with improved solubility and microsomal stability and reduced hERG binding. The build/couple/pair (B/C/P) synthetic strategy, used in the preparation of the original screening library, facilitated medicinal chemistry optimization of the antimalarial lead.

  DOI：

  10.1021/jm500994n
• 作为产物：
  描述：

  在 2,6-二甲基吡啶 、 potassium carbonate 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 、 水 为溶剂， 反应 21.0h， 生成 (2S,3R)-3-(((tert-butyldimethylsilyl)oxy)-4-(4-fluoro-N-methylphenylsulfonamido)-N-(2S)-1-((4-methoxybenzyl)oxy)propan-2-yl)-2-methylbutanamide
  参考文献：
  名称：

  Diversity-Oriented Synthesis-Facilitated Medicinal Chemistry: Toward the Development of Novel Antimalarial Agents

  摘要：

  Here, we describe medicinal chemistry that was accelerated by a diversity-oriented synthesis (DOS) pathway, and in vivo studies of our previously reported macrocyclic antimalarial agent that derived from the synthetic pathway. Structure-activity relationships that focused on both appendage and skeletal features yielded a nanomolar inhibitor of P. falciparum asexual blood-stage growth with improved solubility and microsomal stability and reduced hERG binding. The build/couple/pair (B/C/P) synthetic strategy, used in the preparation of the original screening library, facilitated medicinal chemistry optimization of the antimalarial lead.

  DOI：

  10.1021/jm500994n

文献信息

• [EN] MACROLACTAM COMPOUNDS AND METHODS FOR THE TREATMENT OF MALARIA<br/>[FR] COMPOSÉS MACROLACTAMES ET MÉTHODES DE TRAITEMENT DU PALUDISME
  申请人：BROAD INST INC

  公开号：WO2012142457A3

  公开（公告）日：2013-02-07
• Diversity-Oriented Synthesis-Facilitated Medicinal Chemistry: Toward the Development of Novel Antimalarial Agents
  作者：Eamon Comer、Jennifer A. Beaudoin、Nobutaka Kato、Mark E. Fitzgerald、Richard W. Heidebrecht、Maurice duPont Lee、Daniela Masi、Marion Mercier、Carol Mulrooney、Giovanni Muncipinto、Ann Rowley、Keila Crespo-Llado、Adelfa E. Serrano、Amanda K. Lukens、Roger C. Wiegand、Dyann F. Wirth、Michelle A. Palmer、Michael A. Foley、Benito Munoz、Christina A. Scherer、Jeremy R. Duvall、Stuart L. Schreiber

  DOI：10.1021/jm500994n

  日期：2014.10.23

  Here, we describe medicinal chemistry that was accelerated by a diversity-oriented synthesis (DOS) pathway, and in vivo studies of our previously reported macrocyclic antimalarial agent that derived from the synthetic pathway. Structure-activity relationships that focused on both appendage and skeletal features yielded a nanomolar inhibitor of P. falciparum asexual blood-stage growth with improved solubility and microsomal stability and reduced hERG binding. The build/couple/pair (B/C/P) synthetic strategy, used in the preparation of the original screening library, facilitated medicinal chemistry optimization of the antimalarial lead.